PTPRO plays a dual role in hepatic ischemia reperfusion injury through feedback activation of NF-κB

Jiajie Hou, Yongxiang Xia, Runqiu Jiang, Dianyu Chen, Juan Xu, Lei Deng, Xingxu Huang, Xuehao Wang, Beicheng Sun
Journal of Hepatology 2014, 60 (2): 306-12

BACKGROUND & AIMS: Nuclear factor-κB (NF-κB) activation in hepatocytes and macrophages appeared as a double-edged-sword in hepatic ischemia reperfusion (IR) injury. Protein tyrosine phosphatase receptor type O (PTPRO) was recently identified as a potential activator of c-Src, which can in turn activate the NF-κB pathway. In this study, we aimed to determine the change and function of PTPRO in hepatocytes and macrophages during IR.

METHODS: Clinical patients with benign liver condition undergoing liver surgery were recruited in our study. Wild type (WT) and ptpro(-/-) C57BL/6 mice were processed to construct hepatic IR models. Isolated mouse hepatocytes and macrophages were treated with peroxide or TNFα in vitro.

RESULTS: In human and mouse IR models, PTPRO level was decreased in the early phase but reversed in the late phase. In vitro studies demonstrated that NF-κB up-regulated PTPRO transcription. Using ptpro(-/-) mice and primary cells, we found that PTPRO deficiency resulted in reduction of NF-κB activation in both hepatocytes and macrophages and was correlated to c-Src phosphorylation; PTPRO in hepatocytes alleviated, but PTPROt in macrophages exacerbated IR injury.

CONCLUSIONS: PTPRO activates NF-κB in a positive feedback manner, and plays a dual role in hepatic IR injury.

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